The principal objective of this research program is to gain an understanding of genetic control mechanisms which underly the expression of enzymes in animal cells. This objective is being pursued by genetic and biochemical analyses of mutations which alter the expression of murine glucuronidase. Glucuronidases from high and low activity strains exhibit a difference in structure as determined by heat sensitivity. Preliminary genetic studies suggest that the control of the difference in activity level as well as the difference in structure resides in the glucuronidase structural gene. Immunochemical studies clearly show that the difference in tissue activity levels is directly related to the number of glucuronidase active sites and not to a change in the quality of the active sites. It has been demonstrated that the difference in the number of active sites between high and low activity strains is a function of the rate of synthesis of glucuronidase. Proposed work includes a detailed analysis of the genetic element(s) controlling the structure and rate of synthesis of glucuronidase as well as characterization of the structural difference between the glucuronidases of mutant and normal strains of mice.